Induction of protective cytotoxic T-cell responses by a B-cell-based cellular vaccine requires stable expression of antigen.
Gene Ther
; 16(11): 1300-13, 2009 Nov.
Article
en En
| MEDLINE
| ID: mdl-19641529
ABSTRACT
B-cell-based cellular vaccines represent a promising approach to active immunotherapy of cancer complementing the use of dendritic cells, especially in pediatric patients and patients with low bone marrow reserves. B cells can be easily prepared in large numbers and readily home to secondary lymphoid organs, the primary site of induction of cytotoxic T lymphocyte (CTL) responses. However, most B-cell-based vaccines tested so far failed to induce functional and protective CTLs in in vivo models. Here, we show that B-cells activated through the toll-like receptor-9 (TLR-9) and CD40 up-regulate surface expression of major histocompatibility complex and costimulatory molecules, produce IL-12, and exhibit potent antigen-presenting properties in vitro. Importantly, although administration of peptide-coated or transiently transfected B cells fails to induce immune responses, therapeutic immunization with low numbers of genetically modified B cells stably expressing antigen results in an induction of functional CTLs and protection against the growth of tumor in an animal model. After activation, B cells partially loose their ability to home to organized lymphoid tissue because of the shedding of CD62L; however, this property can be restored by expression of protease-resistant mutant of CD62L. In summary, the data presented in this report suggest that genetically modified activated B cells represent a promising candidate for a cancer vaccine eliciting functional systemic CTLs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timoma
/
Neoplasias del Timo
/
Linfocitos B
/
Linfocitos T Citotóxicos
/
Vacunas contra el Cáncer
Tipo de estudio:
Evaluation_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos